Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells
Abstract Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer’s disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death...
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BMC
2024-11-01
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| Series: | Cellular & Molecular Biology Letters |
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| Online Access: | https://doi.org/10.1186/s11658-024-00657-8 |
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| author | Alp Yigit Özdemir Kateřina Hofbauerová Vladimír Kopecký Jiří Novotný Vladimír Rudajev |
| author_facet | Alp Yigit Özdemir Kateřina Hofbauerová Vladimír Kopecký Jiří Novotný Vladimír Rudajev |
| author_sort | Alp Yigit Özdemir |
| collection | DOAJ |
| description | Abstract Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer’s disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death pathways can be activated in connection with Aβ action, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, alterations in mitophagy, autophagy, and endo/lysosomal functions. In this study, we used a model of differentiated SH-SY5Y cells and applied two different Aβ42 preparations for 2 and 4 days. Although we found no difference in the shape and size of Aβ species prepared by two different methods (NaOH or NH4OH for Aβ solubilization), we observed strong differences in their effects. Treatment of cells with NaOH-Aβ42 mainly resulted in damage of mitochondrial function and increased production of reactive oxygen species, whereas application of NH4OH-Aβ42 induced necroptosis and first steps of apoptosis, but also caused an increase in protective Hsp27. Moreover, the two Aβ42 preparations differed in the mechanism of interaction with the cells, with the effect of NaOH-Aβ42 being dependent on monosialotetrahexosylganglioside (GM1) content, whereas the effect of NH4OH-Aβ42 was independent of GM1. This suggests that, although both preparations were similar in size, minor differences in secondary/tertiary structure are likely to strongly influence the resulting processes. Our work reveals, at least in part, one of the possible causes of the inconsistency in the data observed in different studies on Aβ-toxicity pathways. Graphical Abstract |
| format | Article |
| id | doaj-art-4f151de0003645d299688fddb0eefb4d |
| institution | OA Journals |
| issn | 1689-1392 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cellular & Molecular Biology Letters |
| spelling | doaj-art-4f151de0003645d299688fddb0eefb4d2025-08-20T02:22:20ZengBMCCellular & Molecular Biology Letters1689-13922024-11-0129113310.1186/s11658-024-00657-8Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cellsAlp Yigit Özdemir0Kateřina Hofbauerová1Vladimír Kopecký2Jiří Novotný3Vladimír Rudajev4Department of Physiology, Faculty of Sciences, Charles UniversityInstitute of Physics, Faculty of Mathematics and Physics, Charles UniversityInstitute of Physics, Faculty of Mathematics and Physics, Charles UniversityDepartment of Physiology, Faculty of Sciences, Charles UniversityDepartment of Physiology, Faculty of Sciences, Charles UniversityAbstract Amyloid β42 (Aβ42) plays a decisive role in the pathology of Alzheimer’s disease. The Aβ42 peptide can aggregate into various supramolecular structures, with oligomers being the most toxic form. However, different Aβ species that cause different effects have been described. Many cell death pathways can be activated in connection with Aβ action, including apoptosis, necroptosis, pyroptosis, oxidative stress, ferroptosis, alterations in mitophagy, autophagy, and endo/lysosomal functions. In this study, we used a model of differentiated SH-SY5Y cells and applied two different Aβ42 preparations for 2 and 4 days. Although we found no difference in the shape and size of Aβ species prepared by two different methods (NaOH or NH4OH for Aβ solubilization), we observed strong differences in their effects. Treatment of cells with NaOH-Aβ42 mainly resulted in damage of mitochondrial function and increased production of reactive oxygen species, whereas application of NH4OH-Aβ42 induced necroptosis and first steps of apoptosis, but also caused an increase in protective Hsp27. Moreover, the two Aβ42 preparations differed in the mechanism of interaction with the cells, with the effect of NaOH-Aβ42 being dependent on monosialotetrahexosylganglioside (GM1) content, whereas the effect of NH4OH-Aβ42 was independent of GM1. This suggests that, although both preparations were similar in size, minor differences in secondary/tertiary structure are likely to strongly influence the resulting processes. Our work reveals, at least in part, one of the possible causes of the inconsistency in the data observed in different studies on Aβ-toxicity pathways. Graphical Abstracthttps://doi.org/10.1186/s11658-024-00657-8Amyloid β42Alzheimer´s diseaseCell deathApoptosisNecroptosisReactive oxygen species |
| spellingShingle | Alp Yigit Özdemir Kateřina Hofbauerová Vladimír Kopecký Jiří Novotný Vladimír Rudajev Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells Cellular & Molecular Biology Letters Amyloid β42 Alzheimer´s disease Cell death Apoptosis Necroptosis Reactive oxygen species |
| title | Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells |
| title_full | Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells |
| title_fullStr | Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells |
| title_full_unstemmed | Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells |
| title_short | Different amyloid β42 preparations induce different cell death pathways in the model of SH-SY5Y neuroblastoma cells |
| title_sort | different amyloid β42 preparations induce different cell death pathways in the model of sh sy5y neuroblastoma cells |
| topic | Amyloid β42 Alzheimer´s disease Cell death Apoptosis Necroptosis Reactive oxygen species |
| url | https://doi.org/10.1186/s11658-024-00657-8 |
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